The Significance of Expression of Matrix Metalloproteinases (MMPs) in Intimal Hyperplasia after Ballon Injured Rat Aorta

PURPOSE: Vascular smooth muscle cells (VSMCs) migration and proliferation are important for neointimal formation after arterial injury. Migration of VSMCs requires degradation of basement membrane and extracelluar matrix surrounding the cell, and there is increasing evidence that VSMCs produce extracelluar matrix-degradating proteinases, such as matrix metalloproteinases (MMPs) after arterial injury. To assess the role of MMPs in VSMCs proliferation, migration and intimal thickening, we measured the expression of MMP-2 and MMP-9 in the balloon-injured rat aorta model. METHOD: Twenty-five male Sprague-Dawley rats weighting of 250~300 gm were underwent aortic intimal denudation with 2F balloon catheter. Aorta was harvested at various time intervals of 1, 3, 5, 7, 21 days and then analyzed the MMP expression used by gelatin zymography. Intimal hyperplasia caused by balloon injury was confirmed by microscopic examination. RESULT: MMP-2 (72 kD) was constitutively expressed in the normal aorta and was not increased substantially after injury. But the expression of 62 kd forms, which is activated form of MMP-2, was significantly increased during the period of 5 through 7 days after injury (P<0.05). The expression of MMP-9 (92 kD) was significantly increased at 1st day after injury and diminished thereafter (P<0.05). CONCLUSION: These results suggest that activated MMP-2 (62 kD) and MMP-9 (92 kD) may play an important role in VSMCs migration and formation of intimal hyperplasia after arterial injury. And the activated form of MMP-2 (62 kD) seems to be involved mainly in degradation of basement membrane and matrix.

Effect of Azithromycin in the Treatment of Cyclosporine-induced Gingival Hyperplasia in Renal Transplant Recipient / 대한이식학회지

PURPOSE: Whereas cyclosporine is increasingly used not only in transplantation but also in autoimmune disorders, it may be associated with several side effects. Gingival hyperpalsia is one of the most frequent side effects and has been estimated to occur in 21-30% of all patients receiving the drug and may require surgical correction. Azithromycin is a macrolide antibiotics reported to coincidentally reduce gingival hyperplasia in renal transplant recipients treated for respiratory infections. To confirm the effect of azithromycin in cyclosporine induced gingival hyperplasia we tried clinical use of azithromycin in renal transplant patients with severe gingival hyperplasia. METHODS: Patients (n=9) with cyclosporine induced gingival hyperplasia were selected and took azithromycin for 5 days. Follow-up visits were conducted at week 4 and week 8. Changes in gingival hyperplasia were evaluated by measuring the ratio of clinical crown height and width in each of the four central incisors. RESULTS: Significant improvements were observed in periodontal measurement. The pre-treatment ratio of clinical crown height and width was 1.04+/-0.14 and it was increased to 1.17+/-0.16 in 4 weeks and 1.22+/-0.15 in 8 weeks. 88.9% (8/9) of patients reported an improvement in clinical symptoms. Azithromycin was tolerated and 77.8% (7/9) of patients reported that the treatment was at least somewhat useful. CONCLUSION: Azithromycin treatment for cyclosporine induced gingival hyperplasia is efficacious, cost effective, and has less morbidity compared with gingivectomy.